Annexin A5 prevents amyloid-ß-induced toxicity in choroid plexus: implication for Alzheimer’s disease
Por:
Bartolome F., Krzyzanowska A., de la Cueva M., Pascual C., Antequera D., Spuch C., Villarejo-Galende A., Rabano A., Fortea J., Alcolea D., Lleo A., Ferrer I., Hardy J., Abramov A.Y., Carro E.
Publicada:
1 ene 2020
Resumen:
In Alzheimer’s disease (AD) amyloid-ß (Aß) deposits may cause impairments in choroid plexus, a specialised brain structure which forms the blood–cerebrospinal fluid (CSF) barrier. We previously carried out a mass proteomic-based study in choroid plexus from AD patients and we found several differentially regulated proteins compared with healthy subjects. One of these proteins, annexin A5, was previously demonstrated implicated in blocking Aß-induced cytotoxicity in neuronal cell cultures. Here, we investigated the effects of annexin A5 on Aß toxicity in choroid plexus. We used choroid plexus tissue samples and CSF from mild cognitive impairment (MCI) and AD patients to analyse Aß accumulation, cell death and annexin A5 levels compared with control subjects. Choroid plexus cell cultures from rats were used to analyse annexin A5 effects on Aß-induced cytotoxicity. AD choroid plexus exhibited progressive reduction of annexin A5 levels along with progressive increased Aß accumulation and cell death as disease stage was higher. On the other hand, annexin A5 levels in CSF from patients were found progressively increased as the disease stage increased in severity. In choroid plexus primary cultures, Aß administration reduced endogenous annexin A5 levels in a time-course dependent manner and simultaneously increased annexin A5 levels in extracellular medium. Annexin A5 addition to choroid plexus cell cultures restored the Aß-induced impairments on autophagy flux and apoptosis in a calcium-dependent manner. We propose that annexin A5 would exert a protective role in choroid plexus and this protection is lost as Aß accumulates with the disease progression. Then, brain protection against further toxic insults would be jeopardised. © 2020, The Author(s).
Filiaciones:
Bartolome F.:
Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Group of Neurodegenerative Diseases, Hospital 12 de Octubre Research Institute (imas12), Madrid, Spain
Krzyzanowska A.:
Group of Neurodegenerative Diseases, Hospital 12 de Octubre Research Institute (imas12), Madrid, Spain
de la Cueva M.:
Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Group of Neurodegenerative Diseases, Hospital 12 de Octubre Research Institute (imas12), Madrid, Spain
Pascual C.:
Group of Neurodegenerative Diseases, Hospital 12 de Octubre Research Institute (imas12), Madrid, Spain
Antequera D.:
Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Group of Neurodegenerative Diseases, Hospital 12 de Octubre Research Institute (imas12), Madrid, Spain
Spuch C.:
Neuroscience Translational Group, Galicia Sur Health Research Institute, SERGAS-Universidad de Vigo
Villarejo-Galende A.:
Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Group of Neurodegenerative Diseases, Hospital 12 de Octubre Research Institute (imas12), Madrid, Spain
Neurology service Hospital Universitario 12 de Octubre, Madrid, Spain
Rabano A.:
Department of Neuropathology and Tissue Bank, Unidad de Investigación Proyecto Alzheimer, Fundación CIEN, Instituto de Salud Carlos III, Madrid, Spain
Fortea J.:
Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Institut d’Investigacions Biomediques Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain
Alcolea D.:
Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Institut d’Investigacions Biomediques Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain
Lleo A.:
Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Institut d’Investigacions Biomediques Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain
Ferrer I.:
Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Hospitalet de Llobregat, Spain
Universitat de Barcelona, Hospitalet de Llobregat, Hospitalet de Llobregat, Spain
Hardy J.:
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, United Kingdom
Abramov A.Y.:
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom
Carro E.:
Networking Biomedical Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Group of Neurodegenerative Diseases, Hospital 12 de Octubre Research Institute (imas12), Madrid, Spain
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